Although various anticancer drugs have been developed in an attempt to conquer cancer, a large number of cancer patients ultimately still lose their battle. There are two major causes for this failure: inherited or acquired drug resistance by the cancer cells and side effects due to the poor cell selectivity of anticancer drugs. Multidrug resistance allows cancer cells to survive after receiving the original effective drug, which results in the recurrence of the cancer. Selectivity of anticancer drugs predominantly relies on the proliferation rate difference between normal cells and cancer cells as most cancer cells are fast growing. Unfortunately, many normal cells including cells in the digestive tract, bone marrow, hair follicles, and reproductive system are also fast growing and as such vulnerable to anticancer drugs that target quick proliferating cells. Side effects of anticancer drugs can also compromise the function of the heart, nervous system, and kidneys.
To increase the selectivity of anticancer drugs, various approaches have been explored, including utilizing expression level difference of specific receptors on normal and cancer cells as well as focus on unique physiological properties of tumors such as low pH, high glutathione (GSH) levels, and abnormal metal ion concentrations. Recently, high copper concentration levels in tumors have attracted interest. Copper is an important trace metal that plays critical roles in maintaining normal biological functions. Elevated copper concentration (up to 2-3 fold) is frequently observed in a wide spectrum of tumors including ovarian, breast, cervical, prostate and leukemia and is understood to facilitate tumor angiogenesis. Depletion of copper levels in tumors by use of copper chelators such as D-penicillamine, trientine, and disulfiram has been effective in inhibiting angiogenesis and killing cancer cells both in vitro and in vivo. Unfortunately, due to the non-specific tissue distribution and rapid clearance of the chelators, little or no overall benefit has been observed in those trials.
What are needed in the art are materials and methods that can effectively eradiate cancer cells without damaging healthy tissue.